Tag: statistics

Eur J Radiol. 2022 Jan 11;148:110155. doi: 10.1016/j.ejrad.2022.110155. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to investigate the diagnostic ability of diffusion kurtosis imaging (DKI) -derived parameters combining with clinical data as risk factors for EMVI’s involvement status in rectal adenocarcinoma.

MATERIALS AND METHODS: Preoperative MR examination including DKI and conventional diffusion-weighted imaging (DWI) was performed on 154 rectal adenocarcinoma patients enrolled in this respective study. K_mean, D_mean, and apparent diffusion coefficient (ADC) values were calculated. Clinical information, serum tumor markers, MR and pathological assessment of EMVI were recorded. The Shapiro-Wilk test, two-sample t-test, Mann-Whitney U test, Spearman’s rank-order correlation, univariate and multivariate logistic regression analyses were used for statistical analysis. Receiver operating characteristic (ROC) curve analyses were performed to identify risk factors in EMVI involvement.

RESULTS: Of the 154 patients, pEMVI-positive rectal tumors had significantly higher Kmean values, lower ADC_mean values compared to pEMVI-negative rectal tumors. K_mean values positively correlated with mrEMVI scores, whereas ADC_mean values showed a negative correlation with mrEMVI scores. However, there was no significant correlation between the Dmean values and the mrEMVI scores. Univariate analysis demonstrated increased Kmean values, decreased ADCmean values, nodal involvement, an advanced tumor stage, and a G2 tumor grade were significantly related to the pEMVI of rectal adenocarcinoma. The multivariate analysis demonstrated that the Kmean values, lymph node involvement and an advanced tumor stage (T3) were independent risk factors for EMVI.

CONCLUSION: The potential for diffusion kurtosis imaging as a biomarker for evaluating the EMVI of rectal cancer is feasible, especially given DKI’s capability of detecting tumor heterogeneity noninvasively.

PMID:35045353 | DOI:10.1016/j.ejrad.2022.110155

EBioMedicine. 2022 Jan 16;75:103810. doi: 10.1016/j.ebiom.2021.103810. Online ahead of print.

ABSTRACT

BACKGROUND: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.

METHODS: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 × 10⁵ median Tissue Culture Infectious Dose [TCID₅₀]), one or two injections of a high dose vaccine (1 × 10⁶ TCID₅₀), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298.

FINDINGS: Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment-related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiving the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine.

INTERPRETATION: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.

PMID:35045362 | DOI:10.1016/j.ebiom.2021.103810

Neuron. 2022 Jan 11:S0896-6273(21)01036-9. doi: 10.1016/j.neuron.2021.12.019. Online ahead of print.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability. Extensive conservation, transcriptome, network, and rare variant analyses demonstrated the functional significance of candidate genes in healthy and diseased motor neurons and brain tissues. Genetic convergence between common and rare variation highlighted KANK1 as a new ALS gene. Reproducing KANK1 patient mutations in human neurons led to neurotoxicity and demonstrated that TDP-43 mislocalization, a hallmark pathology of ALS, is downstream of axonal dysfunction. RefMap can be readily applied to other complex diseases.

PMID:35045337 | DOI:10.1016/j.neuron.2021.12.019

Sci Total Environ. 2022 Jan 16:153182. doi: 10.1016/j.scitotenv.2022.153182. Online ahead of print.

ABSTRACT

Non-planned agricultural land abandonment is affecting natural hydrological processes. This is especially relevant in vulnerable arid karstic watersheds, where water resources are scarce but vital for sustaining natural ecosystems and human settlements. However, studies assessing the spatiotemporal evolution of the hydrological responses considering land-use changes and precipitation cycles for long periods are rare in karstic environments. In this research, we selected a representative karstic watershed in a Mediterranean semiarid domain, since in this belt, karst environments are prone to land degradation processes due to human impacts. Geographic Information Systems-based tools and hydrological modeling considering daily time steps were combined with temporal analysis of climate variables (wavelet analysis) to demonstrate possible interactions and vulnerable responses. Observed daily flow data were used to calibrate/validate these hydrological models by applying statistic indicators such as the NSE efficiency and a self-developed index (the ANSE index). This new index could enhance goodness-of-fit measurements obtained with traditional statistics during the model optimization. We hypothesize that this is key to adding new inputs to this research line. Our results revealed that: i) changes in the type of sclerophyllous vegetation (Quercus calliprinos, ilex, rotundifolia, suber, etc.) from 81.5% during the initial stage (1990) to natural grasslands by 81.6% (2018); and, ii) decreases in agricultural areas (crops) by approximately 60% and their transformation into coniferous forests, rock outcrops, sparsely natural grasslands, etc. in the same period. Consequently, increases in the curve number (CN) rates were identified as a result of land abandonment. As a result, an increase in peak flow events jointly with a relevant decrease of the average flow rates (water scarcity) in the watershed was predicted by the HEC-HMS model and verified through the observed data. This research provides useful information about the effects of anthropogenic changes in the hydrodynamic behaviour of karstic watersheds and water resource impacts, especially key in water-scarce areas that depict important hazards for the water supply of related populations and natural ecosystems.

PMID:35045347 | DOI:10.1016/j.scitotenv.2022.153182

Am Heart J. 2022 Jan 16:S0002-8703(22)00006-0. doi: 10.1016/j.ahj.2022.01.006. Online ahead of print.

ABSTRACT

BACKGROUND: Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM.

METHODS: 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation.

RESULTS: Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, p = 0.006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055 – 4.015], p = 0.034 with respect to non-ischemic LGE).

CONCLUSIONS: The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

PMID:35045326 | DOI:10.1016/j.ahj.2022.01.006

J Clin Epidemiol. 2022 Jan 16:S0895-4356(22)00012-9. doi: 10.1016/j.jclinepi.2022.01.010. Online ahead of print.

ABSTRACT

OBJECTIVES: Interrupted Time Series (ITS) are a type of non-randomised design commonly used to evaluate public health policy interventions, and the impact of exposures, at the population level. Meta-analysis may be used to combine results from ITS across studies (in the context of systematic reviews) or across sites within the same study. We aimed to examine the statistical approaches, methods, and completeness of reporting in reviews that meta-analyse results from ITS.

STUDY DESIGN AND SETTINGS: Eight electronic databases were searched to identify reviews (published 2000-2019) that meta-analysed at least two ITS. Characteristics of the included reviews, the statistical methods used to analyse the ITS and meta-analyse their results, effect measures, and risk of bias assessment tools were extracted.

RESULTS: Of the 4213 identified records, 54 reviews were included. Nearly all reviews (94%) used two-stage meta-analysis, most commonly fitting a random effects model (69%). Among the 41 reviews that re-analysed the ITS, linear regression (39%) and ARIMA (20%) were most commonly used; 38% adjusted for autocorrelation. The most common effect measure meta-analysed was an immediate level-change (46/54). Reporting of the statistical methods and ITS characteristics was often incomplete.

CONCLUSION: Improvement is needed in the conduct and reporting of reviews that meta-analyse results from ITS.

PMID:35045318 | DOI:10.1016/j.jclinepi.2022.01.010

J Clin Epidemiol. 2022 Jan 16:S0895-4356(22)00013-0. doi: 10.1016/j.jclinepi.2022.01.008. Online ahead of print.

ABSTRACT

OBJECTIVES: Among ID studies seeking to make causal inferences and pooling individual-level longitudinal data from multiple infectious disease cohorts, we sought to assess what methods are being used, how those methods are being reported, and whether these factors have changed over time.

STUDY DESIGN AND SETTING: Systematic review of longitudinal observational infectious disease studies pooling individual-level patient data from 2+ studies published in English in 2009. 2014, or 2019. This systematic review protocol is registered with PROSPERO (CRD42020204104).

RESULTS: Our search yielded 1,462 unique articles. Of these, 16 were included in the final review. Our analysis showed a lack of causal inference methods and of clear reporting on methods and the required assumptions.

CONCLUSION: There are many approaches to causal inference which may help facilitate accurate inference in the presence of unmeasured and time-varying confounding. In observational ID studies leveraging pooled, longitudinal IPD, the absence of these causal inference methods and gaps in the reporting of key methodological considerations suggests there is ample opportunity to enhance the rigor and reporting of research in this field. Interdisciplinary collaborations between substantive and methodological experts would strengthen future work.

PMID:35045316 | DOI:10.1016/j.jclinepi.2022.01.008

Cell Rep. 2022 Jan 18;38(3):110251. doi: 10.1016/j.celrep.2021.110251.

ABSTRACT

The hypothalamus regulates many innate behaviors, but its development remains poorly understood. Here, we used single-cell RNA sequencing (RNA-seq) and hybridization chain reaction (HCR) to profile multiple stages of early hypothalamic development in the chick. Hypothalamic neuroepithelial cells are initially induced from prethalamic-like cells. Two distinct hypothalamic progenitor populations then emerge and give rise to tuberal and mammillary/paraventricular hypothalamic cells. At later stages, the regional organization of the chick and mouse hypothalamus is highly similar. We identify selective markers for major subdivisions of the developing chick hypothalamus and many previously uncharacterized candidate regulators of hypothalamic induction, regionalization, and neurogenesis. As proof of concept for the power of the dataset, we demonstrate that prethalamus-derived follistatin inhibits hypothalamic induction. This study clarifies the organization of the nascent hypothalamus and identifies molecular mechanisms that may control its induction and subsequent development.

PMID:35045288 | DOI:10.1016/j.celrep.2021.110251

Microsc Res Tech. 2022 Jan 19. doi: 10.1002/jemt.24059. Online ahead of print.

ABSTRACT

We introduce a study of image analysis of kefir biofilms associated with Acai extract prepared by fermentation of fresh kefir grains natural. Atomic force microscopy data were studied, aiming to understand how the concentration of acai berry (Euterpe oleracea Mart.) influences the surface morphology as well as the texture complexity, evaluated by the fractal dimension. The results showed that the superficial morphology was affected by the increase of Acai concentration in the biofilms, as well as the fractal dimension. It has also been observed that the surface of the biofilm presented saturation when concentration changes from 40 to 60 ml. On the other hand, it was observed that the intermediate sample produced with 20 ml of acai berry seems to be the best point for biofilms production that can serve as a skin dressing since other studies related to mechanical properties and in vitro and in vivo tests can confirm this applicability. Thus, the characterization of the surface morphology of kefir biofilms by the evaluation of surface statistical parameters and fractal geometry may provide promising results regarding the applicability of these films.

PMID:35045209 | DOI:10.1002/jemt.24059

J Phys Chem Lett. 2022 Jan 19:864-871. doi: 10.1021/acs.jpclett.1c03374. Online ahead of print.

ABSTRACT

We present measurements of the product-channel branching ratios of the reactions (i) HD⁺ + HD forming H₂D⁺ + D (38.1(30)%) and HD₂⁺ + H (61.9(30)%), (ii) HD⁺ + D₂ forming HD₂⁺ + D (61.4(35)%) and D₃⁺ + H (38.6(35)%), and (iii) D₂⁺ + HD forming HD₂⁺+ D (60.5(20)%) and D₃⁺ + H (39.5(20)%) at collision energies E_coll near zero, i.e., below k_B × 1 K. These branching ratios are compared with branching ratios predicted using three simple models: a combinatorial model (M1), a model (M2) describing the reactions as H-, H⁺-, D-, and D⁺-transfer processes, and a statistical model (M3) that relates the reaction rate coefficients to the translational and rovibrational state densities of the H_nD_3-n⁺ + H/D (n = 0, 1, 2 or 3) product channels. The experimental data are incompatible with the predictions of models M1 and M2 and reveal that the branching ratios exhibit clear correlations with the product state densities.

PMID:35045261 | DOI:10.1021/acs.jpclett.1c03374